2012年10月27日 讯 /生物谷BIOON/ --近日，科研人员证实斑马鱼是一种潜在的独特的可用于检测人类身上个体遗传差异的一类测试工具，并可能有助于新兴领域个性化医学的发展，相关研究由宾夕法尼亚州立大学医学院科学家领导完成。DNA差异或突变导致氨基酸的细微变化，而斑马鱼可以用作模型，来研究这些基因突变产生的生物效应。
现代技术和工具的使用使得个性化药物的发展，也有助于发现生物和个体的遗传差异。病理学教授Keith Cheng医学博士说：个性化医学的一个主要挑战是缺乏一个标准来定义许多重要的在人身上发现的遗传密码基因突变。目前很难区分DNA变化引起我们氨基酸变化后所产生的影响。斑马鱼是不错的选择，因为其作为脊椎动物与人非常相似，其透明度使得这个模型生物的胚胎成为强大的遗传研究工具。
博士后Zurab Tsetskhladze主要测试了两个影响皮肤颜色的基因。Tsetskhladze将正常信使RNA（核糖核酸）注入斑马鱼导致其突变，科学家们希望研究细胞信使RNA产生的蛋白质。
Cheng实验室与斑马鱼的研究，有助于分析人体皮肤颜色的遗传差异。科学家希望确定这些差异在皮肤癌发展中发挥的作用，希望更好地防止人们罹患癌症。研究人员在PLoS ONE发表了他们的研究结果。（生物谷：Bioon.com）
doi:10.1371/journal.pone.0047398
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Functional Assessment of Human Coding Mutations Affecting Skin Pigmentation Using Zebrafish
Zurab R. Tsetskhladze*, Victor A. Canfield, Khai C. Ang, Steven M. Wentzel, Katherine P. Reid, Arthur S. Berg, Stephen L. Johnson, Koichi Kawakami, Keith C. Cheng*
A major challenge in personalized medicine is the lack of a standard way to define the functional significance of the numerous nonsynonymous, single nucleotide coding variants that are present in each human individual. To begin to address this problem, we have used pigmentation as a model polygenic trait, three common human polymorphisms thought to influence pigmentation, and the zebrafish as a model system. The approach is based on the rescue of embryonic zebrafish mutant phenotypes by “humanized” zebrafish orthologous mRNA. Two hypomorphic polymorphisms, L374F in SLC45A2, and A111T in SLC24A5, have been linked to lighter skin color in Europeans. The phenotypic effect of a second coding polymorphism in SLC45A2, E272K, is unclear. None of these polymorphisms had been tested in the context of a model organism. We have confirmed that zebrafish albino fish are mutant in slc45a2; wild-type slc45a2 mRNA rescued the albino mutant phenotype. Introduction of the L374F polymorphism into albino or the A111T polymorphism into slc24a5 (golden) abolished mRNA rescue of the respective mutant phenotypes, consistent with their known contributions to European skin color. In contrast, the E272K polymorphism had no effect on phenotypic rescue. The experimental conclusion that E272K is unlikely to affect pigmentation is consistent with a lack of correlation between this polymorphism and quantitatively measured skin color in 59 East Asian humans. A survey of mutations causing human oculocutaneous albinism yielded 257 missense mutations, 82% of which are theoretically testable in zebrafish. The developed approach may be extended to other model systems and may potentially contribute to our understanding the functional relationships between DNA sequence variation, human biology, and disease.
